Candidate: A PhD in Epidemiology from the Johns Hopkins University, an MD degree, fellowship training in Metabolism, Gerontology and Epidemiology at the NIA has prepared the candidate for an academic career in gerontology and epidemiology. The candidate, an assistant professor at the University of Maryland School of Medicine has studied cardiovascular disease and diabetes in the elderly for the last 11 years. Receipt of this K award will provide the candidate with protected time for research, didactic course work, and mentor based training to retool in genetic epidemiology. This training will allow the candidate to become an independently funded genetic epidemiologist who will study aging and age- related diseases. Alan Shuldiner, MD, Professor of Medicine at the University of Maryland has an active NIH funded genetics research program, has trained many investigators, and will serve as Dr. Sorkin's primary mentor. Dr. Braxton Mitchell, an expert genetic epidemiologist who has recently relocated to the University of Maryland, will serve ad co-mentor. Research: The search for longevity genes in humans is clearly difficult; standard genetic search strategies have met with limited success. We believe that a successful search will have two characteristics: a properly chosen population and a novel study protocol. We propose studying the Old Order Amish, a population whose pedigree is known for 11-14 generations. We will perform affected pairs and quantitative trait linkage (QTL) analyses to identify loci associated with longevity. We hypothesize that: 1) Genetic polymorphisms that influence longevity exist in the genome. 2) The polymorphisms that can result in a long life will interact with each other, other genes, and the environment resulting in pleiotropic expression of the genotype. 3) The polymorphisms extend lifespan by providing protection from age-related diseases such as cardiovascular disease and cancer, and may slow the physiologic processes that we refer to as aging. To identify genetic loci associated with longevity we will recruit Amish probands age 95 and older and their families. We will perform a genome wide scan using short tandem repeat (STR) markers spaced at ~10 cM intervals. We will perform an affected relative pairs linkage analysis of the probands. Aging-related intermediate phenotypes of the probands children will be compared to age and sex-matched subjects (who are unrelated to the probands) in a quantitative trait linkage analysis. The identification of genetic loci associated with longevity will pave the way for molecular studies that will identify longevity genes and the mechanisms by which the genes exert their affects. Knowledge of the molecular basis for longevity and the mechanisms by which longevity genes work may lead to interventions that promote survival in people who did not inherit a genome predisposing to longevity.